France – one of the most influential countries in the development of gene therapy– still stands as a global powerhouse in the field, with top-class institutions, a dense network of expertise and increasing political support. However, financing and manufacturing French gene therapies is proving an issue, meaning that France is facing the prospect of losing out on the full value of its innovations.
A Rich History
France has a long history in gene therapy, as Frédéric Revah, CEO of Genethon, explains. “In the late 1990s, France was leading global research in gene therapy. In 1999, Professor Alain Fischer performed the first successful trial at the Hôpital Necker, demonstrating the possibility of treating immune-deficient babies by gene therapy, transferring corrective genes in their immune system cells. In this way, the immune functions were restored, and the treated children, who had originally an expected life-span of three to four years constrained in a completely sterile bubble, were able to live and grow.”
Genethon itself – a laboratory created by the patient organization AFM-Telethon (the French Muscular Dystrophy Association) – can be considered a pioneer in the gene therapy field. Revah adds, “Today, at a time when the field of gene therapy is experiencing exponential growth, Genethon is probably a pioneer, as it is one of the oldest organizations completely focused on this field in the world. We started in 1996-1997, when the industrial interest in gene therapy was decreasing. At the beginning of the 1990s, there had been some interest in gene therapy, as it was seen as a possible way to treat any disorder. Soon, it became clear that the field would not deliver such results, and the industrial players withdrew. However, AFM-Telethon firmly believed that gene therapy could be a game-changer in rare genetic disease, and, through Genethon, invested heavily in the field.”
Strength to Strength
This tradition is being carried on today, notably in the Paris region. Genopole – France’s largest biotech cluster, bringing together 87 biotech companies, 17 academic research laboratories, and 27 shared-access technology platforms – is aiming to position itself as an internationally renowned reference in genome sequencing. As Jean-Marc Grognet, the cluster’s general manager puts it, “Genopole is an expert in genome sequencing and has one of the largest facilities for genome sequencing in Europe. We have all the pieces of the puzzle to build the next generation of medication – education, research, and industry.”
He continues, “In Genopole we have four main fields of interest: personalized medicine, innovative therapeutic solutions using cell and gene therapies, digital genomics, biotechnologies related to environmental matters, and agri-food. The research being done at Genopole puts us at the forefront of innovation.”
Government funding for gene therapy research is steadily increasing. As, Faten Hidri, VP for higher education & research for the Paris Region (Ile de France), confirms, “We have put in place a new, more international scientific commission. This scientific commission has redefined the Domaines d’Intérêt Majeur (Domains of Major Interests). The DMIs are the main vehicle through which research is financed. Different labs federate themselves around a common research project which they present to the commission in order to access funding that totals EUR 16 (USD 18) million. 11 fully-licensed DMIs have been selected and two other so-called emergent DMIs for which the project has been deemed interesting but needs more structure. Among these 13 DMIs, four revolve around health: gene therapy, infectiology, innovative biological techniques and longevity (emergent).”
Collaboration between public and private actors is also on the rise. Hidri declares, “we try to bridge the gap between academic and industrial research through a number of initiatives. For instance, the laboratories that work on the DMIs are required to collaborate with incubators and competitiveness clusters. They do not have to be asked twice since they already are craving working hand in hand with small innovative companies and larger groups.”
Made in France?
However, France currently lacks the manufacturing footprint necessary to commercialise its discoveries in the gene therapy field. As Genethon’s Revah laments, “France’s strength lies in the fact that there is a strong expertise on the scientific and the clinical side of things. What we are missing is the industrial element attached to it… If we are not able to innovate in manufacturing, products invented in France will have to be produced elsewhere. It would be an incredible loss in economic value for our country.”
Cognizant of this risk, in 2016 AFM-Telethon created YposKesi – an industrial platform exclusively dedicated to the manufacturing and development of gene and cell therapy products, serving both Genethon as well as third parties as a CDMO. Revah, who is also the president of YposKesi, states that “ideally, YposKesi will be the new nucleus allowing the crystallization of knowledge in the [French gene therapy] value chain.”
Finding the Funds
Another problem facing the French industry is a lack of domestic funding, with French innovations having to be sold off to firms from overseas. Revah adds that, “certainly, an issue in both the French and European markets is the lack of funds. A lot of our products have been licensed to US companies, just because they have the money, or they are in the position to raise substantial funds. If we want to keep these products in Europe, we have to find ways to raise funds here.”
Phillipe Archinard, CEO of French gene engineering specialist Transgene, part of Institut Mérieux, feels that, although France has a healthy venture capital (VC) scene, there is not enough funding for French biotechs to move up the value chain. He observes that “It is clear that France is quite good at seeding startups compared to other parts of the world. There is a lot of money to be invested but as companies move forward into the growth stage, the funding gap becomes greater as more capital is needed for development. The more money startups need, the more difficult it becomes to get it – a problematic loop. There are very few significant VCs in France which work together, which limits the opportunities available. I believe there is a duty to foster a wider variety of approaches. All in all, there is substantial financing for seeding in France but for too few to scale up.”
Archinard does though issue a clarion call to potential investors in French cell and gene therapy start-ups, highlighting the huge potential in the sector. “There is a momentous innovation movement everywhere, here in France but also in China for instance,” he states. “You do not have to always go to the USA to find ingenuity as some people mistakenly think. There are different ways in the world nowadays and we have to learn to look for them!”
